april06.html

University of Virginia Nutrition
Support
E-Journal Club
April 2006

Greetings,

This month our journal club was held in conjunction with our
bi-annual Nutrition Support Forum. Our Forum is a ½ day affair where
dietitians from the region bring interesting cases and we review
articles in an informal setting. Our trainees this month hailed
from Columbia Tennessee, Fresno California, and our own Virginia Beach.
Here is a picture of the group that participated in our forum.

This was an open-label crossover trial in 10 consecutive patients
with acute renal failure that were receiving both parenteral nutrition
(PN) and dialysis in a specialized renal intensive care unit.
Patients received 24 hours of protein-free PN (D20) and then either
lower calorie PN (30 calories/kg) or higher calorie PN (40 calories/kg)
for 3 days, and then were crossed over to the other regimen for 3 days
without a washout period. The population had a mean age of 72
(range 60-83), mean APACHE II score of 27.1 (range 23-34) and 8/10 were
mechanically ventilated. All patients received 1.56gm protein
/kg.

Major Results reported by authors:

The authors reported that there was no significant difference
between the two calorie levels in regards to nitrogen balance, protein
catabolic rate, or rate of urea generation. However serum glucose
level, insulin requirements (approx 20 units per day) and serum
triglyceride level were all significantly increased in the higher
calorie group. Two patients were excluded from the analysis
because one patient expired, and one patient had significantly elevated
serum triglyceride level (both patients from high-calorie
group). Mean serum glucose and triglycerides were significantly
elevated in the high-calorie group compared to the low-calorie
group.

Authors Conclusions:

The authors reported that in critically ill patients, increasing
calorie provision from 30 kcals/kg to 40 kcals/kg does not improve
nitrogen balance, and may increase the risk of nutrition-related side
effects.

Evaluation:

This was a small study in terms of patient numbers (n = 10).
Also, there is potential for bias to be introduced in a crossover study
in an ICU where, time can influence the results in patients that are
improving or new infections can develop quickly, changing nitrogen
balance results. Our major observation was that
both calorie levels likely exceeded actual
calorie expenditure, and thus it is not surprising that they did not
see a significant difference in nitrogen balance or urea generation
rate. The mean age of the patients was 72.6 years, with a range
of 60-82 years, therefore actual calorie expenditure may have been
closer to 25 calories per kg. The difference in serum glucose between
the groups was statistically significant (p,.05), but not clinically
overwhelming (mean of 123mg/dl in low-cal, versus 143mg/dl in
high-cal). However the high-calorie group did receive an average
of 20 more units of insulin per 24 hours, and triglycerides were
significantly elevated in the high-calorie group, suggesting that the
high-calorie group was receiving more calories than they could
utilize. It would be very interesting to see if there would have
been a difference if one group was fed with permissive underfeeding
(20-22 calories/kg) and the other group received 35 calories per
kg. We encounter obese, critically ill patients with increasing
frequency, and the dilemma of finding the optimum calorie level for
these patients is compounded in the setting of acute renal
failure. Unfortunately, it would be inappropriate to translate
the results of this study to mean that adequate calories do not have a
nitrogen-sparing effect compared to hypocaloric feeding. The
group felt that this study only showed that there is no overwhelming
advantage to overfeeding calories in terms of nitrogen balance or urea
generation.

Take home message:

There is no advantage to overfeeding calories in terms of nitrogen
balance or urea generation.

This was a non-blinded study of 100 patients with acute lung
injury. Patients were randomized to receive enteral feedings with
a formula containing gamma-linolenic acid (GLA) and eicosapentanoic
acid (EPA) enriched with antioxidants (Oxepa); or an isocaloric and
isonitrogenous control formula (Pulmocare). Primary outcomes were
change in oxygenation and "breathing patterns" assessed at days 4, 7
and 14. Secondary outcomes were length of ventilation, length of
ICU stay, length of hospital stay, and in-hospital mortality.

Major Results reported by authors:

The researchers reported that both groups reached 75% of goal
feeding (REE X 1.2) in approx. 2 days, with no difference between
groups. Oxygenation was significantly higher at days 4 and 7 in
the EPA+GLA group compared to the control, but was not significantly
different at day 14. Tidal volume and PEEP values were not
significantly different between the groups. Static compliance
improved in the GLA + EPA group from day 1 through day 7, but decreased
in the control group. Day 7 static compliance was significantly
higher in the EPA +GLA group. Median length of ventilation was
decreased when analyzed as hours free from ventilation. Overall
survival and length of stay was not significantly different between the
groups.

Authors Conclusions:

The authors concluded that in patients with acute lung injury, a
diet enriched with EPA + GLA may be beneficial for gas exchange,
respiratory dynamics, and mechanical ventilation requirements.

Evaluation:

We learned of an important correction to this article that needs to
be discussed. A criticism of this article would have been that
the older formulation of Pulmocare was used as the control formula for
this study, based on the formula composition listed in Table 1.
This was one of the primary criticisms of the Gadek study (1) - that
the control formula was extremely rich in Omega-6 fatty acids.
However, we have learned from our astute Ross representative that the
control formula actually used in this study was, in fact, the
current formulation of Pulmocare, which contains only 25% of the
fat calories (14% of total calories) as Omega-6 polyunsaturated
fat. Reportedly, a correction in Critical Care Medicine is
forthcoming.

Our first observation is that this is not a blinded study. In
any unblinded study there is potential for unintentional bias to enter
into the study. The second observation is that this study was not
analyzed on an intention-to-treat basis. The researchers simply
discarded the results of 5 patients that were dropped from the study (2
patients placed on corticosteroids, and 3 due to severe
diarrhea). This is especially concerning in an unblinded study in
which 4 of the patients were dropped from the experimental group.
It is important to analyze all patients randomized, especially if
severe diarrhea occurred more in the experimental group, which might
limit how many patients could be "helped" by the tested product.
The length of ventilation was reported as significantly less in the
GLA+EPA group on day 7, when it was reported as
hours off vent. However, when viewed
as days of ventilation it is 6.68 days in the experimental and
6.95 days in the control group - this is not a clinically significant
difference in ventilator days.

There are significant improvements in oxygenation (PaO2/FiO2) and
static compliance in the EPA+GLA group, however it does not appear that
these changes resulted in a clinically meaningful improvement in
overall outcome in terms of days on ventilator or survival. The
authors also reported that a post-hoc analysis of the patients who
survived showed a trend towards a reduction in the length of
ventilation and time in the ICU.

Take home message:

Methodological limitations (unblinded, not intention to treat) of
this study limit it's impact. In addition, there was no
clinically significant outcome advantage of the experimental formula in
terms of days on the ventilator or overall survival in patients with
ALI.

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